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Abstract

This study examined the effects of acute tobacco smoking on cerebral oxygenation and autonomic function in 28 male, habitual smokers of shorter young smokers (YSM) or longer middle-aged smokers (MSM) smoking history. Following baseline testing, participants undertook a smoking protocol involving the consumption of two cigarettes within 15 min. Measures of cerebral oxygenation and autonomic function were collected before, during, and 0 min, 30 min, 1 h, and 4 h post-smoking. Tissue saturation index (TSI) for MSM was greater than YSM during cigarette consumption (p < 0.05). Moreover, MSM observed significant within-group changes for TSI during and post-cigarette consumption (p < 0.05). Further, MSM observed an increase in low frequency (LF) band from 30 min to 1 h post-consumption, followed by a decline, whereas elevations above MSM were observed in YSM at 4 h (p < 0.05). Both MSM and YSM showed a decrease in high-frequency (HF) band post-cigarette, while increased LF/HF ratio post-consumption was observed in YSM. A decline in the standard deviation of RR intervals, post-cigarette consumption was evident in MSM (p < 0.05). Moreover, the root mean square of RR interval in both groups similarly decreased following cigarette consumption (p < 0.05). Acute smoking affects heart rate variability, suggestive of vagal withdrawal, and maybe indicate an effect of smoking history. Additionally, prolonged smoking history alters cerebral microcirculatory responses to acute tobacco exposure in MSM.

Keywords

Tobacco near-infrared spectroscopy autonomic function

Introduction

Active or passive exposure to tobacco smoke exposes multiple organs, particularly those of the pulmonary and cardiovascular systems to repeated chemical insult,¹ whereby profound effects on many biological systems can ensue.^2,3 As a result, underlying pathogenesis of chronic diseases including cardiovascular disease (CVD), cancers, pulmonary diseases, and diabetes can develop.^4,5 Systemic diseases resulting from regular exposure to tobacco smoke are thought to occur via increased vascular permeability, reduced endothelium-dependent vasodilatation,^3

–6 prolonged increases in blood pressure and heart rate (HR), and changes in cerebral and peripheral hemodynamics.^7
–9 These cardiovascular outcomes are accompanied by an imbalance between oxidant stress and antioxidant defense, increased platelet aggregation, increased cellular adhesion molecules, inflammation, and sheer stress.^3,10 Collectively, the abovementioned factors can increase the risk for cardiovascular events.¹¹ While the role of chronic tobacco smoking on endothelial dysfunction and autonomic control have been well documented,^12
–14 it is not well known whether the mechanisms precipitating such changes can be attributed to age and smoker history or whether these changes are a result of the acute responses to repeated smoking exposure.

Among notable physiological changes from tobacco smoking is the disruption of normal autonomic nervous system balance, characterized by sympathetic hyperactivity and attenuated parasympathetic activity.¹² This autonomic imbalance may be attributed to nicotine exposure,¹⁵ which stimulates the release of catecholamines, epinephrine, and norepinephrine,^7,15 subsequently stimulating cardiovascular events.^15,16 In turn, this sympathetic stimulation also increases myocardial contractility, cardiac output, stroke volume, and peripheral vasoconstriction.¹⁷ Although the autonomic effects of chronic tobacco smoking have been studied extensively, the acute effects are less well known.^12,16,18 Given the unfavorable effects of tobacco smoking on cardiovascular health, particularly autonomic regulation, it seems important to determine the acute microcirculatory and sympathetic responses to smoking. Moreover, given the absence of longitudinal data, a comparison of acute autonomic responses to smoking in those with a longer compared to shorter smoking history may provide insight into the pathophysiological pathways contributing to cardiopulmonary disease.

In addition to nicotine, tobacco smokers are exposed to a myriad of chemical compounds, which may impose many deleterious effects on cardiovascular function.⁴ The presence of compounds such as carbon dioxide and nitric oxide exerts vasodilatory effects, whereas compounds such as nicotine act as a vasoconstrictor.¹⁹ Consequently smoke exposure is suggested to alter cerebral hemodynamics, increasing the risk of cerebrovascular disease.⁹ Previous literature from transcranial Doppler ultrasound,²⁰ near-infrared spectroscopy (NIRS),⁹ and positron emission tomography¹⁹ suggests that regional cerebral blood flow (rCBF) velocity is increased in response to tobacco smoking^19,20 and temporarily reduces vasomotor reactivity.²⁰ Additionally, tobacco smoke has been reported to reduce peripheral microcirculation.⁸ Such changes in cerebral and peripheral hemodynamics may present as a precursor for early endothelial injury, ultimately predisposing to the development of atherosclerosis.⁸ However, despite the abundance of literature concerning many deleterious effects of tobacco smoking on the aspects of cardiovascular physiology, the effects of tobacco smoking on cerebral oxygenation are less understood and could prove pivotal in advancing knowledge about smoking and the progression of systemic disease.

The acute sympathetic and hemodynamic responses to tobacco smoking are associated with adverse cardiovascular events.^11,21 Currently, there is limited literature describing the acute effects of tobacco smoking on autonomic regulation, particularly in regard to the length of smoking history.¹² Additionally, the acute effects of tobacco smoking on microcirculation as determined by NIRS are less understood. Collectively, it is unknown whether the acute changes in sympathetic activity and microcirculation are influenced by the length of smoking history as a surrogate for the lack of longitudinal data. Therefore, the aim of this study was to determine the effect of acute tobacco smoke inhalation on measures of microcirculation and autonomic function. A further aim was to determine whether a longer smoking history alters the aforementioned responses compared to a relatively shorter smoking history. It was hypothesized that smokers with a longer smoking history would present with greater autonomic imbalance and reduced microcirculation compared to those with a shorter smoking history.

Methods

Participants

The study cohort consisted of 14 smokers with a relatively short smoking history (YSM; 22.0 ± 1.6 years of age; 2.86 ± 1.91 pack-years) and 14 smokers with a longer smoking history (MSM; 33.3 ± 7.7 years of age; 12.15 ± 9.61 pack-years). The delimited age ensured groups would have differences in smoking history but would still be of a similar state of health to ensure differences in fitness, and other variables of aging were not confounding factors. Participants reported as apparently healthy and free from any known metabolic, cardiovascular or pulmonary disease, immunological irregularities, or other conditions. Any participant who was confirmed as having any of these conditions or taking potentially confounding medications was excluded from the study. The self-reported smoking history for the YSM and MSM populations was 5.2 ± 1.7 and 14.6 ± 6.5 years of smoking and 12.3 ± 6.8 and 15.8 ± 7.3 cigarettes per day, respectively. Prior to the commencement of the study, all participants were required to provide written and verbal consent following an outline of all procedures and measures. This study conformed to the Declaration of Helsinki and was approved by the Research in Human Ethics Committee at Charles Sturt University.

Study overview

Prior to involvement in the study, participants were required to undergo a medical screening, completed an adult pre-exercise screening system healthy history questionnaire and the Fagerstrom test for nicotine dependence.²² If participants satisfied the study inclusion criteria, they were then enrolled into the study. Participants completed an initial familiarization prior to a baseline testing session, which included anthropometry, a graded exercise text (GXT), spirometry, and a dual-energy X-ray absorptiometry (DXA) scan. Following approximately 7 days rest, participants returned to the laboratory and were required to partake in a single testing session. Participants were instructed to successively smoke two cigarettes of the same brand (Winfield Blue, 12 mg tar, 1 mg nicotine) within 15 min; with HR, blood pressure and cerebral oxygenation measured throughout the smoking period and before and after (0 min, 30 min, 1 h, and 4 h) cigarette consumption. To ensure standardized responses, following the smoking protocol, participants remained in the laboratory with the researchers until 4 h post-measures in a fasted and rested state, with no additional exposure to tobacco smoke (i.e. environmental).

Baseline testing

Following a prior familiarization with all procedures, participants reported to the laboratory between 05:30 h and 08:00 h, rested and fasted for a baseline testing session. Stature (stadiometer: customized, Bathurst, Australia), body mass (HW 150 K; A&D, Bradford, Massachusetts, USA), and waist and hip circumferences (steel tape; EC P3 metric graduation, Australia) were obtained for analysis of body composition based on standardized techniques. Body mass index was calculated from mass and stature, while waist and hip circumferences provided a waist to hip ratio. In addition, a supine DXA scan was conducted for the determination of body composition (XR800; Norland, Cooper Surgical Company, Trumbull, Connecticut, USA). Scanning resolution and speed were set at 6.5 × 13.0 mm and 130 mm s⁻¹, respectively. Whole body scans were analyzed (Illuminatus DXA, version 4.2.0, Norland, Cooper Surgical Company, Trumbull, Connecticut, USA) for total body lean mass and total body fat mass and are reported in absolute and relative terms.

Resting blood pressure was measured through a commonly used indirect technique involving the use of an aneroid sphygmomanometer and stethoscope (Welch Allyn, Arden, North Carolina, USA), while participants were also fitted with an HR monitor (Rs800cx; Vantage NV, Polar, Finland) to obtain a measure of resting HR. Additionally, a baseline blood sample was collected to determine fasting glucose and total cholesterol.

Participants then performed a GXT on an electronically braked cycle ergometer (LODE Excalibur Sport, LODE BV, Groningen, The Netherlands) for the determination of VO_2peak. The younger population began the incremental GXT at 100 W and increase by 25 W every minute until volitional exhaustion, whereas the middle-aged population began the GXT at 25 W and increase 25 W every minute. A measure of HR was obtained every minute until the completion of the GXT. Pulmonary gas exchange was measured by determining oxygen (O₂) and carbon dioxide (CO₂) concentrations and ventilation to calculate VO₂ using a metabolic gas analysis system (Parvo Medics, True2400, East Sandy, Utah, USA). The system was calibrated according to the manufacturer’s instructions. This involved the pneumotachometer calibration using a 3 L syringe. The gas analyzers were calibrated using a two-point fully automated process involving room air and gas calibration for fractional gas concentration with a gravimetric gas mixture of known concentrations (CO₂, 4.1 (0.1)%; O₂, 15.7 (0.2)%).

Experimental protocol: Cigarette consumption

Participants reported to the laboratory between 05:30 h and 08:00 h in a fasted and rested state for the completion of the smoking protocol. Participants were instructed to smoke two filtered cigarettes (Winfield Blue, 12 mg tar, 1 mg nicotine) within 15 min in a private but open area near the laboratory. Participants remained seated throughout the protocol with no or minimal movements to ensure standardized measurements. Normal smoking behavior was encouraged during the consumption of the two cigarettes, adequacy of smoking ensured by visual observation by the research team. The selection of the acute smoking protocol was chosen based upon previous research by Van der Vaart et al.²³ who administered two cigarettes of the same brand within 30 min. Given the lack of acute smoking research, this was the guideline for selection of the smoking protocol used here. Further, selection of the brand of brand of cigarette was also based upon research published by Van der Vaart et al.,²³ involving two cigarettes of 12 mg tar, 1 mg nicotine. The selected brand in the current study is considered average in terms of nicotine dose, and prior questioning regarding smoking habits deemed this brand an appropriate brand and nicotine content among the selected group.

Near-infrared spectroscopy

A continuous wave NIRS instrument was used as a noninvasive tool for measuring microcirculatory changes in oxygenated ([HbO₂]), deoxygenated ([HHb]), and total cerebral hemoglobin ([THb]) concentrations (Artinis Medical System, Oxymon MKIII, Zetten, The Netherlands). NIRS data were recorded at 10 Hz for the duration of the smoking protocol; a further 3 min recording was obtained at 30 min, 1 h, and 4 h post-cigarette consumption. During all NIRS sampling, participants were required to be seated in an upright position and following a 5 min stabilization period, normalized breathing patterns were ensured. NIRS data collected during the acute smoking protocol were normalized against approximately 120 s of baseline data, collected prior to each measurement in a rested state, seated in an upright position. For each time point, the NIRS probe was placed over the left prefrontal cortex between Fp1 and F3 (international EEG 10-20 system) and placement was adjusted approximately <5 mm for individual variance. The NIRS probe was affixed with double-sided adhesives, and the inter-optode distance was fixed at 3.5 cm via a black plastic spacer. A modified Beer–Lambert law was applied to determine oxygenated and deoxygenated hem concentration, based on the absorption coefficient of continuous wavelength infrared light (856 and 794 nm) and age-dependent differential path-length factors. Total hemoglobin was calculated via the sum of oxygenated and deoxygenated hemoglobin concentrations to give an indication of regional blood volume. Further, tissue saturation index (TSI) was calculated as a ratio of oxygenated to total hemoglobin concentrations.

HR and blood pressure

Participants wore a HR monitor (Rs800cx; Vantage NV) for the attainment of HR and heart rate variability (HRV) during the testing protocol. The collection of HRV was paralleled with the collection and timing of NIRS variables. HRV was collected throughout the smoking protocol and for 3 min at each subsequent post-measure, following a 5-min stabilization period. Following recording, HR files were downloaded to Polar software (Polar Protrainer 5; Polar Electro Oy, Kempele, Finland) via infrared; after visual inspection, occasional ectopic beats were identified and replaced with interpolated (linear) adjacent RR interval values. HRV analysis was performed using HRV software (Kubios 2.1; Biosignal Analysis and Medical Imaging Group, Finland). Both time and frequency domain analyses were performed. The mean RR interval, the standard deviation of RR interval (SDNN), and the root mean square of RR interval differences (rMSSD) were analyzed. A power spectral analysis using Welch’s periodgram provided frequency domain parameters (Kubios 2.1; Biosignal Analysis and Medical Imaging Group). Components of power spectrum were computed with the following bandwidths: high frequency (HF; 0.15–0.4 Hz), low frequency (LF; 0.04–0.15 Hz), thus providing the LF/HF ratio. Data are expressed as raw values for both frequency and time domain parameters.

Blood pressure was obtained through a commonly used indirect technique involving the use of an aneroid sphygmomanometer and stethoscope (Welch Allyn). The cuff was placed on the upper arm over the brachial artery and above the antecubital fossa. The head of the stethoscope was placed over the antecubital fossa. The cuff was inflated to occlude the brachial artery, then gradually deflated while the assessor listens for the appearance of Korotkoff sounds, using the first and fifth stages as systole and diastole. The measurement was repeated following sufficient rest, and the two readings averaged to provide an individual’s blood pressure.²⁴

Statistical analysis

Normal distribution was determined by Shapiro–Wilk’s test, and non-normally (rMSSD, LF and HF) distributed data were logarithmically transformed prior to analysis All data are reported as mean ± standard deviation (SD). Repeated measures analysis of variance (ANOVA; Condition × Time) was used to determine within- and between-group differences. Where a group interaction was noted, one-way ANOVA tests were applied to determine the source of significance. Significance was set at p < 0.05. All statistical procedures were performed using Predictive Analytic Software (Statistical Package for the Social Sciences for Windows version 18.0, Chicago, Illinois, USA).

Results

Baseline variables for anthropometric variables and smoking history are reported in Table 1. The MSM group had significantly (p = 0.001) greater smoking history in terms of years of smoking and pack-years than YSM. However, the dependence level (based upon the Fagerstrom Test for Nicotine Dependence)²² and volume of cigarette smoke did not differ between groups (p = 0.19). There were no differences between the groups for VO_2peak (p = 0.26), though the MSM group demonstrated greater absolute and relative fat mass than YSM (p = 0.00). Further, YSM had higher FVC and FEV_1.0 at baseline compared to MSM (p = 0.007; p = 0.027).

Table 1.

Mean ± SD baseline descriptive, anthropometric, DXA, biochemistry, aerobic fitness, and smoking variables within the young smoker (n = 14) and middle-aged smoker (n = 14) populations.

Anthropometric and descriptive data	YSM	MSM
Age (years)	22.0 ± 1.57	33.27 ± 7.75^a
Height (m)	1.82 ± 0.07	1.77 ± 0.07
Weight (kg)	81.78 ± 12.07	81.22 ± 12.87
VO_2peak (mL kg⁻¹ min⁻¹)	36.67 ± 3.06	33.93 ± 8.74
Final stage (Watts; GXT)	275 ± 36.69	230 ± 46.48
Waist circumference (cm)	84.46 ± 8.44	87.67 ± 8.92
Hip circumference (cm)	98.22 ± 5.95	101.54 ± 8.34
Waist to hip ratio	0.86 ± 0 .05	0.86 ± 0.06
% Fat mass	15.62 ± 5.78	24.75 ± 6.76^a
Lean mass (kg)	63.03 ± 9.05	59.02 ±6.61
Fat mass (kg)	12.37 ± 5.32	20.68 ± 6.83^a
Smoking variables
Years of smoking	5.21 ± 1.72	14.62 ± 6.55^a
Cigarettes per day	12.31 ± 6.81	15.79 ± 7.34
Pack-years	2.86 ± 1.91	12.15 ± 9.61^a
Fagerstrom score	2.31 ± 1.38	2.48 ± 1.28

DXA: dual-energy X-ray absorptiometry; GXT: graded exercise text; SD: standard deviation.

^a p < 0.05: significantly different to YSM.

There were no observed differences between groups for HR or BP at rest or across the protocol (Figure 1). Additionally, there were no within-condition changes in SBP for YSM or MSM. However, an increase in DBP from pre to post for YSM (p = 0.043) was observed, that was not present in MSM, despite a decline in DBP from 1 h to 4 h in MSM (p = 0.041). No between-group differences were observed for HR. However, both groups showed a within-condition increase for HR from pre- to post-cigarette consumption followed by a decline at 30 min, which continued only for YSM to 1 h post (p = 0.00; p = 0.022).

Figure 1.

Mean ± SD heart rate and blood pressure pre, end of cigarettes 1 and 2 (EC1 and EC2 or post), 30 min, 1 h, and 4 h post-cigarette consumption for younger smokers and older smokers. *p < 0.05: significantly different between YSM and MSM; ^# p < 0.05: significantly different within condition for YSM; ^¥ p < 0.05: significantly different within condition for MSM. SD: standard deviation.

The time domain parameters for HRV are presented in Figure 2. There were no baseline differences in rMSSD or SDNN between YSM and MSM. MSM showed a significant decline in SDNN post-cigarette consumption (p = 0.009), which was not significant in YSM. Both groups showed elevations in SDNN at 30 min post-consumption (p = 0.04; p = 0.004). Further, rMSSD in both groups decreased following cigarette consumption (p = 0.04; p = 0.01). The frequency domain parameters are presented in Figure 3. Despite no significant baseline differences for HF, LF, or LF/HF, only MSM observed a decrease immediately post-cigarette consumption followed by an increase LF from 30 min to 1 h post-consumption, followed by a decline thereafter (p = 0.04; p = 0.02); conversely, YSM observed higher values for the raw power of LF at 4 h compared to MSM (p = 0.02). Both groups observed within-group changes for HF, with a decrease from pre to immediately post (p = 0.02; p = 0.05), followed by an increase at 30 min (p = 0.01; p = 0.00) and only a decline observed for MSM (p = 0.04). For LF/HF, an increase in YSM was observed from pre to post (p = 0.00), which was not observed in MSM (p = 0.54), although both groups observed a decline from immediately post to 30 min (p = 0.00; p = 0.01). Further, MSM observed a significant increase from 30 min to 1 h post (p = 0.03), which occurred later for YSM (1–4 h). Values for YSM remained above pre at 4 h (p = 0.01).

Figure 2.

Mean ± SD time domain parameters of HRV pre, post, 1 h, and 4 h post-cigarette consumption for younger smokers and older smokers. *p < 0.05: significantly different between YSM and MSM; ^# p < 0.05: significantly different within condition for YSM; ^¥ p < 0.05: significantly different within condition for MSM. SD: standard deviation; HRV: heart rate variability.

Figure 3.

Mean ± SD frequency domain parameters of HRV pre, post, 1 h, and 4 h post-cigarette consumption for younger smokers and older smokers. *p < 0.05: significantly different between YSM and MSM; ^# p < 0.05: significantly different within condition for YSM; ^¥ p < 0.05: significantly different within condition for MSM. SD: standard deviation; HRV: heart rate variability.

In regard to NIRS responses, there were no significant differences in [HbO₂], [HHb], or [THb] between groups at baseline or throughout the protocol (Figure 4). However, for MSM, TSI was greater than YSM during consumption of the second cigarette (p = 0.048; p = 0.01). While YSM showed within-group changes from pre to start of first cigarette in TSI (p = 0.05), this was not different to MSM (p = 0.25). Further, while YSM showed no within-group change for [HHb], values for MSM increased immediately from pre to start of cigarette consumption followed by a decrease to post-cigarette consumption (p = 0.023; p = 0.002; p = 0.002). Following cigarette consumption, elevations in [HHb] to baseline were observed to 1 h in MSM (p = 0.021), however were not observed in YSM. Finally, no within-group changes were observed for either group for [HbO₂].

Figure 4.

Mean ± SD cerebral oxygenation ([HbO2]), deoxygenation ([HHb]), TSI, and total hemoglobin ([THb]) pre, start of cigarettes 1 and 2 (SC1 and SC2), end of cigarettes 1 and 2 (EC1 and EC2) post, 30 min, 1 h, and 4 h post-cigarette consumption for younger smokers and older smokers. *p < 0.05: significantly different between YSM and MSM; ^# p < 0.05: significantly different within condition for YSM; ^¥ p < 0.05: significantly different within condition for MSM. SD: standard deviation; HRV: heart rate variability; TSI: tissue saturation index.

Discussion

This study aimed to elucidate what effects acute tobacco smoking had on autonomic and hemodyamic changes in smokers, with particular respect to comparison of shorter versus longer smoking histories. The findings revealed that acute cigarette smoking may result in prolonged vagal withdrawal, which may be indicative of sympathetic hyperactivity; this was evidenced in YSM by decreases in HF and an increase in the LF/HF ratio. A further finding indicates that acute tobacco smoking increases TSI and [HHb] during the cigarette consumption, followed by declines post-cigarette consumption among in [HHb] among MSM, but not YSM, which also suggests an effect of smoking history on cerebral hemodynamics (Figure 4).

While the adverse effects of tobacco smoking are many, changes in autonomic control and hemodynamics may be among the most important for the determination of cardiovascular risk. Chronic tobacco smoking is known to augment sympathetic dominance¹⁸ and reduce vagal modulation;²⁵consequently such alterations in autonomic balance have been associated with adverse clinical outcomes.¹⁶ However, despite the abundance of literature concerning, the chronic effects of smoking on HRV, only a few studies have reported on the acute effects of tobacco smoke on autonomic control.^16,18 Mendonca et al.¹⁸ reported both raw HF and LF power to decrease following smoking, with the LF/HF ratio increased, suggesting sympathetic dominance. Findings from the current study reveal that even brief exposure to tobacco smoke produces notable changes in sympathovagal balance, as reflected by decreases in HF and LF power and elevated LF/HF ratio in YSM following cigarette consumption. Further, the sympathetic response was delayed, or inhibition of parasympathetic tone was present in YSM following acute smoke exposure (as represented by the delayed LF/HF peak when compared to MSM). Our study observed similar findings to that of Karakaya et al.¹⁶ who reported acute smoking increased the LF/HF ratio and reduced the mean RR intervals, SDNN, and rMSSD within 5 min of smoking a cigarette. Further, time domain parameters suggest reduced vagal modulation, particularly among MSM, who similarly to Karakaya et al.¹⁶ observed a reduction in SDNN post-cigarette consumption. Additionally, rMSSD decreased following cigarette consumption in both groups, which is indicative of reductions in the parasympathic component of autonomic control.²⁶ Moreover, in a study by Hayano et al.²⁷ concerning HRV parameters in heavy, moderate, and non-smokers, taking into account the respiratory component, suggested that heavy smoking (∼12 years and >25 cigarettes per day) results in acute and transient decreases in vagal cardiac control and that heavy smoking results in long-term reductions in vagal cardiac control in habitual smokers with a shorter smoking history.

Tobacco smoke has powerful excitatory effects of the SNS,¹¹ which may be a direct effect of nicotine via the stimulation and blocking of autonomic ganglia or direct impairment of baroreflex function.^27,28 Increased sympathetic activity has pro-arrhythmic, atherosclerotic, and thrombotic actions which may be involved in the elevated cerebrovascular risk observed in smokers.²⁵ Consequently, results from the current study are reflective of acute vagal withdrawal which may be suggestive of sympathetic hyperactivity. While the precise mechanism behind sympathetic dominance remains elusive, acute responses may be useful in understanding how tobacco smoking results in the disruption of autonomic balance.

Smoking is an important risk factor for cerebrovascular diseases.²⁹ While chronic tobacco smoking is associated with reduced cerebral blood flow, literature concerning the acute responses to smoking is inconsistent.^9,30 Previous studies have reported that tobacco smoking decreases rCBF, as measured by transcranial Doppler sonography;^9,20 however, the effects of tobacco smoking on cerebral microcirculation as determined by NIRS remain less well known. Regardless, this methodology could assist in elucidating microcirculatory changes associated with the heightened cerebrovascular risk in smokers. While Terborg et al.⁹ reported no change in deoxygenated hemoglobin with smoking, Pucci et al.³⁰ reported deoxygenated hemoglobin to increase after 5 min of smoking and additionally observed concomitant increases in oxygenated hemoglobin. The current study revealed that despite the initial increase in TSI in YSM, it was comparatively greater during cigarette consumption in smokers with a longer smoking history (MSM). Furthermore, smoking induced increases in [HHb] in MSM during the cigarettes followed by declines, but no notable changes in YSM. In contrast to the present study, Siafaka et al.⁸ reported no change in peripheral hemoglobin saturation as a result of smoking. However, we found that [HbO₂] remained unchanged, while [HHb] was increased during the consumption of cigarettes followed by a decrease [HHb] in MSM. Such a finding would indicate that smoking induces a transient desaturation in the MSM. If this is the case, an increase in [HHb] in the prefrontal cortex without simultaneous increases in [HbO₂] might compromise neuronal activity in this group of MSM. In the present study, the observed increase in TSI and [HHb] in MSM during cigarette consumption may be attributed to carbon monoxide (CO) exposure, which due to the high affinity of CO to hemoglobin, causes a leftward shift in the hemoglobin–oxygen dissociation curve.⁸ Moreover, during cigarette smoking, approximately 5–22 mg of CO are emitted.³¹ Consequently given that the absorption of carboxyhemoglobin by red light is of a similar wavelength to [HbO₂], the presence of CO may interfere with readings of [HbO₂]. While the acute effects of smoking report conflicting findings, previous literature did not define groups based upon smoking history, which could be a limiting factor. The younger smoker group in the present study observed no significant changes in cerebral hemodynamic parameters, suggesting when isolated by age, long-term smoking may alter cerebral oxygenation and the associated hemodynamics.

While previous studies have reported tobacco smoking to increase cerebral blood flow velocity and reduce vasomotor reactivity²⁰ as demonstrated by transcranial Doppler sonography⁹ given the changes to autonomic control, it seems imperative to determine whether the changes to autonomic control are reflected in changes to cerebral microcirculation. While an increase in sympathetic dominance was resultant from acute cigarette smoking, these effects were not reflected in cerebral oxygenation of either YSM or MSM. Previous vasomotor studies using NIRS methodology suggest that changes in cerebral oxygenation are representative of changes in cerebral blood flow.³² However, in the present study, despite the observed increase in sympathetic drive, elevations in cerebral oxygenation did not occur, which may be attributed to compounds such as CO or the reduction of bioactive nitric oxide that act as a vasodilator, and is reduced by chronic smoking.^33,34 Granted the effect of tobacco smoking on the vasculature can be influenced by multiple biochemical and hemodynamic factors, the determination of microcirculatory and autonomic age-based responses to smoking may further our understanding, particularly in regard to the negative longitudinal effects of smoking.

Despite these findings, certain limitations must be acknowledged. The respiratory rate of smokers may present as a limitation to the current study, as there is an established relationship between breathing frequency and HRV parameters. Brown et al.³⁵ reported a reduction in the absolute power of LF and HF components, suggesting that breathing may have an effect on parameters of HRV. As a means to control this, participants were seated in an upright position, where breathing patterns were normalized before the collection of data. Further, while the authors acknowledge the LF/HF ratio data can indicate higher coefficient of variation,³⁶ it may provide indications and directions for future research in the area. A further limitation to the study is the age of the MSM, while an older population is desirable, many presented with pre-existing medical conditions, thus the MSM on average maybe younger than desired. However, despite age being a limitation, the MSM had comparable health status to YSM, thus eliminating any age-related constraints.

In conclusion, the present study indicates an acute effect of tobacco smoking on both the frequency and time domain parameters of HRV, suggestive of sympathetic dominance, and may further indicate an effect of smoking history, particularly in regard to LF/HF in YSM. A further finding is the observed changes in [HHb] and TSI in MSM which may suggest that prolonged tobacco smoking alters cerebral microcirculatory responses to smoke, which ultimately may increase the risk of cerebrovascular disease and suppressed neuronal activity at specific instances. While the measures are novel and represent a small portion of the physiological responses to tobacco smoking, these findings may provide future direction into the acute microcirculatory and sympathetic effects of smokers who present with different smoking histories.

Footnotes

Acknowledgments

The authors would like to acknowledge the institutional staff at the University Exercise Physiology Laboratories Bathurst NSW for their assistance. They would also like to acknowledge the participants for their participation in the study.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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